The objective of the proposed experiments is to further describe the chemical changes in the extracellular fluid of the brain associated with neuronal function. Voltammetric and ion-selective electrodes will be used to simultaneously monitor KC1-induced electrochemical signals in the caudate-putamen (CPu) of the rat. The studies will focus on the timing and magnitude of [K+]o, [Ca2+]o and field potential signals associated with the release of dopamine (DA) and the regulation of these signals by the nigral dopaminergic cell body region. The selectivity of the voltammetric electrodes will be tested in the CPu by comparing the chronoamperometric response of Nafion-coated and uncoated electrodes in animals treated with pargyline, pargyline and haloperidol, alpha methyl-p=tyrosine and FLA-63. These treatments should provide evidence for the in vivo reliability of the Nafion-coated electrodes to selectively detect cationic amines. Once the selectivity of the voltammetric electrodes has been described, multiple electrode assemblies will be used to monitor the ionic changes associated with neurotransmitter release as a function of KC1 stimulus concentrations. The KC1 will be pressure ejected approximately 750mu from the recording electrodes. The signals will be analyzed for concentration and timing relationships. It is hoped that the ionic thresholds and a concentration-dependent relationship for DA release can be established from this study. The final component of this study will examine the effect of lidocaine inactivation of the substantia nigra in the ipsilateral and contralateral CPu in rats unilaterally lesioned with 60HDA. Comparison of the ionic and voltammetric signals in these animals should indicate the importance of DA release in the propagation of the KC1-induced voltammetric signals. The studies described in this proposal will increase the available information relatively to the ionic changes influencing neural activity in the extracellular environment. Studying these effects in the CPu and altering the activity of the substantial nigra may provide fundamental information describing the chemical regulation of the nigro-striatal pathway. Information derived from such studies should provide a clearer understanding of the relation of ion movement to neurotransmitter release in pathenogenic conditions such as epileptic seizures, ischemia and spreading depression.